Chlorine isotope effects

A diagrammatic illustration of the effect of an isotope pattern on a mass spectrum. The two naturally occurring isotopes of chlorine combine with a methyl group to give methyl chloride. Statistically, because their abundance ratio is 3 1, three Cl isotope atoms combine for each Cl atom. Thus, the ratio of the molecular ion peaks at m/z 50, 52 found for methyl chloride in its mass spectrum will also be in the ratio of 3 1. If nothing had been known about the structure of this compound, the appearance in its mass spectrum of two peaks at m/z 50, 52 (two mass units apart) in a ratio of 3 1 would immediately identify the compound as containing chlorine. 

Kinetic isotope effects also show a dependence upon the reactivity of the electrophile. Thus some reactions, e.g. positive chlorination, show no isotope effect whereas others, e.g. sulphonation, do show an isotope effect. There are two ways of visualising the reasons for this and they are closely related. Very... 

The first step, as we have already seen (12-3), actually consists of two steps. The second step is very similar to the first step in electrophilic addition to double bonds (p. 970). There is a great deal of evidence for this mechanism (1) the rate is first order in substrate (2) bromine does not appear in the rate expression at all, ° a fact consistent with a rate-determining first step (3) the reaction rate is the same for bromination, chlorination, and iodination under the same conditions (4) the reaction shows an isotope effect and (5) the rate of the step 2-step 3 sequence has been independently measured (by starting with the enol) and found to be very fast. With basic catalysts the mechanism may be the same as that given above (since bases also catalyze formation of the enol), or the reaction may go directly through the enolate ion without formation of the enol ... 

Westaway KC, T Koerner, Y-R Fang, J Rudzinski, P Paneth (1998) A new method of determining chlorine kinetic isotope effects. A a/ Chem 70 3548-3552. 

Valnes of have been measnred for a number of polychlorinated biphenyl (PCB) congeners and applied to a nnmber of commercial PCB mixtures. Both the number and the position of the chlorine snbstitnents affected the depletion of C, and this reflected the mannfacturing procednres that involved kinetic isotope effects as well as the source of the biphenyl starting material (Jarman et al. 1998). It was snggested that this could be applied to determine the source of PCBs in the environment. 

Isotope ratios for and Cl were measured for the aerobic degradation of dichlorometh-ane by a methanotroph MC8b (Heraty et al. 1999). Values of the fractionation factor (a) were 0.9586 for carbon and 0.9962 for chlorine, and kinetic isotope effects were 1.0424 for carbon and 1.0038 for chlorine. 

Lewandowicz A, J Rudzinski, L Tronstad, M Widersten, P Ryberg, O Matsson, P Paneth (2001) Chlorine isotope effects on the haloalkane dehalogenase reaction. J Am Chem Soc 123 4550-4555. 

Kinetic isotope effects have not been observed for chlorination, and only rarely for bromination, i.e. the reactions normally follow pathway [2a] like nitration. In iodination, which only takes place with iodine itself on activated species, kinetic isotope effects are the rule. This presumably arises because the reaction is readily reversible (unlike other halogenations), loss of I occurring more often from the a complex (14) than loss of H, i.e. k, > k2 ... 

Although 28Mg is farther from the band of stability than is 27Mg, the former is an even-even nuclide while the latter is an even-odd nuclide. As we have seen earlier, even-even nuclides tend to be more stable. Consequently, the even-even effects here outweigh the fact that 28Mg is farther from the band of stability. Another interesting case is shown by considering these isotopes of chlorine ... 

Although GC-C-IRMS systems that can measure the chlorine isotopic composition of individual chlorinated hydrocarbons are currently unavailable, it is clear that chlorine isotope analysis is also a useful technique to consider for study [614,677,678]. Measurement of chlorine stable isotope ratios in natural samples such as rocks and waters has become routine [626,679,680], but few measurements of chlorine isotopes in chlorinated aliphatic hydrocarbons have been reported [614]. A chlorine isotope effect was found in ferf-butyl chloride [681], demonstrating that 37Cl is more strongly bound to carbon than is 35Cl. Significant differences in the <5i7Cl values of some atmospheric chlorinated... 

Obviously, there is an isotope effect on the vibrational frequency v . For het-eroatomic molecules (e.g. HC1 and DC1), infrared spectroscopy permits the experimental observation of the molecular frequencies for two isotopomers. What does one learn from the experimental observation of the diatomic molecule frequencies of HC1 and DC1 To the extent that the theoretical consequences of the Born-Oppenheimer Approximation have been correctly developed here, one can deduce the diatomic molecule force constant f from either observation and the force constant will be independent of whether HC1 or DC1 was employed and, for that matter, which isotope of chlorine corresponded to the measurement as long as the masses of the relevant isotopes are known. Thus, from the point of view of isotope effects, the study of vibrational frequencies of isotopic isomers of diatomic molecules is a study involving the confirmation of the Born-Oppenheimer Approximation. 

For heavy atom isotope effects tunneling is relatively unimportant and the TST model suffices. As an example the dehalogenation of 1,2-dichloroethane (DCE) to 2-chloroethanol catalyzed by haloalkane dehalogenase DhlA is discussed below. This example has been chosen because the chlorine kinetic isotope effect for this reaction has been computed using three different schemes, and this system is among the most thoroughly studied examples of heavy atom isotope effects in enzymatic reactions. 

The haloalkane dehalogenase DhlA mechanism takes place in two consecutive Sn2 steps. In the first, the carboxylate moiety of the aspartate Aspl24, acting as a nucleophile on the carbon atom of DCE, displaces chloride anion which leads to formation of the enzyme-substrate intermediate (Equation 11.86). That intermediate is hydrolyzed by water in the subsequent step. The experimentally determined chlorine kinetic isotope effect for 1-chlorobutane, the slow substrate, is k(35Cl)/k(37Cl) = 1.0066 0.0004 and should correspond to the intrinsic isotope effect for the dehalogenation step. While the reported experimental value for DCE hydrolysis is smaller, it becomes practically the same when corrected for the intramolecular chlorine kinetic isotope effect (a consequence of the two identical chlorine labels in DCE). 

Another approach to modeling the chlorine kinetic isotope effect of this reaction has been carried out using a true QM/MM scheme. 

O Neil JR (1986) Theoretical and experimental aspects of isotopic fractionation. Rev Mineral 16 1-40 Oi T (2000) Calculations of reduced partition function ratios of monomeric and dimeric boric acids and borates by the ab initio molecular orbital theory. J Nuclear Sci Tech 37 166-172 Oi T, Nomura M, Musashi M, Ossaka T, Okamoto M, Kakihana H (1989) Boron isotopic composition of some boron minerals. Geochim Cosmochim Acta 53 3189-3195 Oi T, Yanase S (2001) Calculations of reduced partition function ratios of hydrated monoborate anion by the ab initio molecular orbital theory. J Nuclear Sci Tech 38 429-432 Paneth P (2003) Chlorine kinetic isotope effects on enzymatic dehalogenations. Accounts Chem Res 36 120-126... 

The ratio of products (36) and (37) from VNS of hydrogen (Pe) and substimtion of halogen (Px), respectively (Scheme 4), will depend on the strength and concentration of base, provided that the elimination is a kinetically important step in the VNS reaction, namely Pr/Px = kikE[B]/k-ikx. The influence of base will decrease until a constant value Ph/Px = k /kx is reached as kslB] k i. This has been demonstrated for 4-chloronitrobenzene, which undergoes exclusive substimtion of chlorine unless strong base is present to favour the VNS process. The deuterium isotope effect for VNS hydroxylation by Bu OOH, determined as me ratio of H versus D substitution of l-deutero-2,4-dinitrobenzene, varied from 7.0 0.3 to 0.98 0.01 as the base in NH3 was changed from NaOH to Bu OK me former value is consistent with a rate determining E2 process. 

Kaiser, E. W and T. J. Wallington, Comment on Inverse Kinetic Isotope Effect in the Reaction of Atomic Chlorine with C2H4 and C2D4, J. Phys. Chem. A, 102, 6054-6055 (1998). 

Stutz, J., M. J. Ezell, A. A. Ezell, and B. J. Finlayson-Pitts, Rate Constants and Kinetic Isotope Effects in the Reactions of Atomic Chlorine with n-Butane and Simple Alkenes at Room Temperature, J. Phys. Chem., 102, 8510-8519 (1998). 

Kinetic data, interpretation, 40, 44, 78 Kinetic isotope effects, 46 carbon, 47 chlorine, 47... 

A review of methods of synthesis of aromatic iodo compounds has appeared offering considerable information of potential value to research chemists wishing to prepare iodoheterocycles (84RCR343). Iodination differs from chlorination and bromination in that a much less reactive electrophile (and a much larger one) is involved. The second step of the reaction is usually at least partially rate-determining. Isotope effects are noted in the iodination of indole [68AC(R) 1435], and the transition state resembles the Wheland intermediate more than in chlorination and bromination. 

---